title: Phase II clinical study of modified FOLFOX7 (intermittent oxaliplatin administration) plus bevacizumab in patients with unresectable metastatic colorectal cancer-CRAFT study.
abstract: OBJECTIVE
  Continuous treatment with FOLFOX therapy is associated with peripheral nerve toxicity, and to improve this inconvenient side effect various methods of administration are being investigated. A regimen of intermittent oxaliplatin administration by continuous infusion therapy, i.e., modified FOLFOX7 (mFOLFOX7) + bevacizumab, was designed with the goal of alleviating severe peripheral nerve disorders and hematological toxicity. A phase II clinical study was conducted to evaluate the efficacy and safety of this regimen.
  
  
  METHODS
  Previously untreated patients were assigned to mFOLFOX7 (oxaliplatin 85 mg/m(2), levofolinate [l-LV] 200 mg/m(2), 5-fluorouracil [5-FU] 2400 mg/m(2)) + bevacizumab (5 mg/kg) administered every 2 weeks for 8 cycles, maintenance without oxaliplatin for 8 cycles, and reintroduction of mFOLFOX7 + bevacizumab for 8 cycles or until disease progression. Progression free survival (PFS) following the first dose (PFS 1) and following reintroduction of oxaliplatin (PFS 2) were used as indices for assessing the efficacy of intermittent administration.
  
  
  RESULTS
  Fifty-two patients were enrolled, with median age of 64 years (range, 36-74). Median PFS 1 was 11.8 months (95 % confidence interval [CI], 9.5 to 13.7), median time to treatment failure was 10.3 months (95 % CI, 5.6 to 12.1), percentage of patients with neutropenia of grade 3 or higher was 7.8 %, and percentage with peripheral nerve disorders was 3.9 %. Response rate was 50 %, and 84.4 % of patients who started modified simplified LV5FU2 + bevacizumab were reintroduced to oxaliplatin.
  
  
  CONCLUSIONS
  By excluding 5-FU bolus administration and administering bevacizumab continuously the mFOLFOX7 + bevacizumab regimen with preplanned withdrawal of oxaliplatin showed high tolerability and prevented severe peripheral neuropathy and neutropenia without reducing efficacy.
authors.affiliation: Department of Surgery, Teikyo University Chiba Medical Center, 3426-3 Anesaki, Ichihara City, Chiba, Japan, 299-0111, tohru_tezuka@tokyo-hmt.jp.
authors.forename: Tohru
authors.initials: T
authors.lastname: Tezuka
authors.forename: Chikuma
authors.initials: C
authors.lastname: Hamada
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Ishida
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Ooshiro
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsuoka
authors.forename: Shingo
authors.initials: S
authors.lastname: Kawasaki
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Mishima
authors.forename: Kotaro
authors.initials: K
authors.lastname: Maeda
authors.forename: Junichi
authors.initials: J
authors.lastname: Sakamoto
authors.forename: Keiji
authors.initials: K
authors.lastname: Koda
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000068258:Bevacizumab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D000068258:Bevacizumab; D002955:Leucovorin; D005472:Fluorouracil